Human papillomavirus type 16 and risk of preinvasive and invasive vulvar cancer: Results from a seroepidemiological case-control study

Objective: To examine whether human papillomavirus (HPV) type 16 is involved in the etiology of vulvar carcinomas. Methods: We studied 142 histologically confirmed cases of vulvar intraepithelial neoplasia (VIN) grade 3 and invasive vulvar cancer and 126 community controls. In addition to a detailed questionnaire through which we obtained information on putative risk factors for vulvar cancer, blood samples were collected from participating subjects and tested for the presence of antibodies to HPV-16 virus-like particles. Data were analyzed by logistic regression. Results: Subjects positive for HPV-16 antibodies were at a 5.3-fold increased risk of vulvar neoplasia (95% confidence interval [CI] 2.5, 11.1), and subjects with high antibody levels were at a 20-fold increased risk of disease (95% CI 5.4, 76.7). A stronger association between HPV-16 seropositivity and disease was observed for VIN grade 3 (odds ratio [OR] 13.4; 95% CI 3.9, 46.5) than for invasive disease (OR 2.9; 95% CI 0.94, 8.7), and for invasive tumors, there was a suggestion that the association was stronger for women diagnosed with squamous carcinoma of basaloid and/or warty types (OR 3.8; 95% CI 0.76, 18.9) than for those diagnosed with keratinizing squamous cell carcinomas (OR 1.6; 95% CI 0.33, 7.4). Number of sexual partners and herpes simplex virus type 2 seropositivity remained as independent risk factors for vulvar neoplasia after control for confounding by HPV-16. The risk associated with HPV-16 seropositivity was higher among smokers (OR 8,5; 95% CI 3.8, 19) than among nonsmokers (OR 3.4; 95% CI 0.85, 13). Conclusion: Our results confirm that HPV is associated with vulvar carcinomas. Findings also suggest the possibility that other sexually transmitted agents might be involved in the etiology of some vulvar tumors and that smoking may be an important cofactor involved ill the etiology of HPV-related vulvar tumors. Evaluation of the role of HPV types other than HPV-16 in the etiology of vulvar cancer is needed, and additional efforts aimed at further elucidating the role of smoking and other cofactors in this disease process are warranted.